Role of plant homeodomain finger protein 8 in P19 embryonic carcinoma cells revealed by genome editing and specific inhibitor.

Plant homeodomain finger protein 8 (PHF8) is a histone demethylase that regulates the expression of various genes. PHF8 targets repressor histone markers and activates gene expression. Although PHF8 has been involved in X-linked mental retardation and certain types of cancers, the role of PHF8 remains largely unknown, and its relevance to the pathogenesis of these diseases is also uncertain.

Total colectomy for poorly controlled hypokalaemia due to Gitelman syndrome.

Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by dysfunction of the thiazide-sensitive sodium-chloride cotransporter, which leads to hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. Patients with GS show varied clinical features due to hypokalaemia: tetany, muscle weakness, periodical paralysis and constipation, which is one of the most frequent ones. This paper presents the case of a woman in her 40s referred to our endocrinology department for severe hypokalaemia.

Comprehensive In Silico Functional Prediction Analysis of CDKL5 by Single Amino Acid Substitution in the Catalytic Domain.

Cyclin-dependent kinase-like 5 (CDKL5) is a serine/threonine protein kinase whose pathological mutations cause CDKL5 deficiency disorder. Most missense mutations are concentrated in the catalytic domain. Therefore, anticipating whether mutations in this region affect CDKL5 function is informative for clinical diagnosis.

HDAC8 is implicated in embryoid body formation via canonical Hedgehog signaling and regulates neuronal differentiation.

Histone acetylation and deacetylation are associated with diverse biological phenomena via gene transcription, and histone deacetylases (HDACs) regulate protein deacetylation. HDAC8 is associated with childhood neurological disorders that develop in the uterus and may contribute to neurodevelopment. In our previous studies, we found that HDAC8 regulates neuronal differentiation in P19 pluripotent embryonic carcinoma cells (P19EC cells) by regulating embryoid body (EB) formation.

Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population.

Objective: To assess whether eldecalcitol, an active vitamin D analogue, can reduce the development of type 2 diabetes among adults with impaired glucose tolerance.

Design: Double blinded, multicentre, randomised, placebo controlled trial.

Setting: Three hospitals in Japan, between June 2013 and August 2019.

p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis.

Background: The neuronal ceroid lipofuscinosis (NCL) are a group of autosomal recessive neurodegenerative disorders that are characterized by the accumulation of ceroid lipofuscins. The NCLs are categorized into four classes based on the age of onset. Kufs disease is a rare adult-onset NCL caused by mutations in the CLN6 gene, which is rarely observed in the Japanese population.

Zinc finger protein 483 (ZNF483) regulates neuronal differentiation and methyl-CpG-binding protein 2 (MeCP2) intracellular localization.

Rett syndrome (OMIM #312750) is a developmental neurological disorder that is caused by a mutation in methyl-CpG-binding protein 2 (MeCP2). MeCP2 localizes to the nucleus, binds to methylated DNA, and regulates gene expression during neuronal development. MeCP2 assembles multiple protein complexes and its functions are controlled by interactions with its binding partners.

Establishment of a Simple Method for Inducing Neuronal Differentiation of P19 EC Cells without Embryoid Body Formation and Analysis of the Role of Histone Deacetylase 8 Activity in This Differentiation.

P19 pluripotent embryonic carcinoma (EC) stem cells are derived from pluripotent germ cell tumours and can differentiate into three germ layers. Treatment of these cells in suspension culture with retinoic acid induces their differentiation into neurons and glial cells. Hence, these cells are an excellent in vitro model to study the transition from the upper blastoderm to the neuroectoderm.

Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder.

Cyclin-dependent kinase-like 5 (CDKL5, also known as STK9) is a serine/threonine protein kinase originally identified in 1998 during a transcriptional mapping project of the human X chromosome. Thereafter, a mutation in was reported in individuals with the atypical Rett syndrome, a neurodevelopmental disorder, suggesting that CDKL5 plays an important regulatory role in neuronal function. The disease associated with mutation has recently been recognised as CDKL5 deficiency disorder (CDD) and has been distinguished from the Rett syndrome owing to its symptomatic manifestation.

In Silico Study of Rett Syndrome Treatment-Related Genes, , , and , by Evolutionary Classification and Disordered Region Assessment.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (), which has multiple functions such as binding to methylated DNA or interacting with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 () or forkhead box protein G1 () correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We investigated the evolution and molecular features of MeCP2, CDKL5, and FOXG1 and their binding partners using phylogenetic profiling to gain a better understanding of their similarities.

Yokukansan, a Kampo medicine, enhances the level of neuronal lineage markers in differentiated P19 embryonic carcinoma cells.

Yokukansan (YKS), a traditional Japanese Kampo medicine, affects neurological and psychiatric disorders. It ameliorates hippocampal neurogenesis in animals. However, its effect on neuronal cell differentiation remains unclear.

Straightforward and rapid method for detection of cyclin-dependent kinase-like 5 activity.

Cyclin-dependent kinase-like 5 (CDKL5) is a serine/threonine protein kinase, with its gene mutation leading to a neurodevelopmental disorder. Pathogenic point mutations are mostly observed within the catalytic domain of CDKL5, therefore loss of catalytic activity may be related to disease onset. However, this hypothesis has rarely been demonstrated.

HDAC8 regulates neural differentiation through embryoid body formation in P19 cells.

Histone acetylation and deacetylation correlate with diverse biological phenomena through gene transcription. Histone deacetylases (HDACs) regulate deacetylation of histones and other proteins. However, as a member of the HDAC family, HDAC8 function during neurodevelopment is currently unknown.

Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study.

Introduction: Recent research suggests that vitamin D deficiency may cause both bone diseases and a range of non-skeletal diseases. However, most of these data come from observational studies, and clinical trial data on the effects of vitamin D supplementation on individuals with pre-diabetes are scarce and inconsistent. The aim of the Diabetes Prevention with active Vitamin D (DPVD) study is to assess the effect of eldecalcitol, active vitamin D analogue, on the incidence of type 2 diabetes among individuals with pre-diabetes.

A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome.

Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function.

A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets.

X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets.

Incidence of type 2 diabetes in pre-diabetic Japanese individuals categorized by HbA1c levels: a historical cohort study.

Objective: Reported incidence of type 2 diabetes estimated at the pre-diabetic stage differs widely (2.3-18.1% per year).

Generation of rat induced pluripotent stem cells using a plasmid vector and possible application of a keratan sulfate glycan recognizing antibody in discriminating teratoma formation phenotypes.

Induced pluripotent stem cells (iPSCs) offer an invaluable tool for biological research and regenerative medicine. We report establishment of rat iPSCs (riPSCs) using a plasmid vector encoding four transcription factors, Oct3/4, Sox2, c-Myc and Klf4. Although all riPSC clones were generated and cultured under the same conditions, expressed hallmark pluripotency markers and differentiated successfully in vitro, the expression of a keratan sulfate glycan epitope with unique properties defined by R-10G antibody varied in the riPSC clones.

Allele-specific real-time polymerase chain reaction as a tool for urate transporter 1 mutation detection.

Allele-specific polymerase chain reaction (ASPCR) method has long been applied for the detection of nucleotide variations and genotyping, which are detected by the presence or absence of DNA amplification PCR products. Recently, Real-Time PCR genotyping has fast developed and offered a rapid method of detecting mutations without the need of gel electrophoresis as with ASPCR. Here, we describe an easy and rapid touchdown real-time PCR method for the detection of nucleotide variations.

Idursulfase enzyme replacement therapy in an adult patient with severe Hunter syndrome having a novel mutation of iduronate-2-sulfatase gene.

Mucopolysaccharidosis II (Hunter syndrome), a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS), has variable clinical phenotypes. Total by nearly 400 different mutations have been identified in IDS gene from patients with Hunter syndrome. Herein, we reported a patient who has a novel mutation in IDS gene with a severe clinical phenotype.

Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial.

Background: Statins are not effective in reducing atherosclerotic plaques of the abdominal aorta, and accumulating evidence suggests that bisphosphonates have the potential to induce the regression of atherosclerotic plaques of the abdominal aorta.

Methods And Results: A prospective, randomized, open-label, blinded-end-point trial involving 108 participants with hypercholesterolemia was conducted. Participants received 20 mg atorvastatin daily, 400 mg etidronate daily, or both drugs daily.

Simple and rapid detection method for the mutations in SLC22A12 that cause hypouricemia by allele-specific real-time polymerase chain reaction.

Background: Hypouricemia is a disorder that serum urate level is less than 2.0 mg/dl, and relatively common in the Japanese population, where the main genetic cause of hypouricemia is W258X and R90H mutations in human urate trasnsporter 1(SLC22A12). Small scale screening has relied on time-consuming traditional ways like polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Tandem configurations of variably duplicated segments of 22q11.2 confirmed by fiber-FISH analysis.

22q11.2 duplication syndrome has recently been established as a new syndrome manifesting broad clinical phenotypes including mental retardation. It is reciprocal to DiGeorge (DGS)/velo-cardio-facial syndrome (VCFS), in which the same portion of the chromosome is hemizygously deleted.

Effect of atorvastatin and etidronate combination therapy on regression of aortic atherosclerotic plaques evaluated by magnetic resonance imaging.

Aim: Although statins have been well documented to induce the regression of thoracic aortic plaques, a similar effect of statins on abdominal aortic plaques has not been observed.We aimed to explore whether a statin in combination with a bisphosphonate was effective in the regression of abdominal aortic plaques, which are more likely to be calcified.

Methods: Eighty-seven patients with hypercholesterolemia were assigned to the atorvastatin (ATR)+etidronate (ETD) group (n = 45) or ATR group (n = 42).